Mortality and Case Fatality Due to Visceral Leishmaniasis in Brazil: A Nationwide Analysis of Epidemiology,Trends and Spatial Patterns

Background

Visceral leishmaniasis (VL) is a significant public health problem in Brazil and several regions of the world. This study investigated the magnitude, temporal trends and spatial distribution of mortality related to VL in Brazil.

Methods

We performed a study based on secondary data obtained from the Brazilian Mortality Information System. We included all deaths in Brazil from 2000 to 2011, in which VL was recorded as cause of death. We present epidemiological characteristics, trend analysis of mortality and case fatality rates by joinpoint regression models, and spatial analysis using municipalities as geographical units of analysis.

Results

In the study period, 12,491,280 deaths were recorded in Brazil. VL was mentioned in 3,322 (0.03%) deaths. Average annual age-adjusted mortality rate was 0.15 deaths per 100,000 inhabitants and case fatality rate 8.1%. Highest mortality rates were observed in males (0.19 deaths/100,000 inhabitants), <1 year-olds (1.03 deaths/100,000 inhabitants) and residents in Northeast region (0.30 deaths/100,000 inhabitants). Highest case fatality rates were observed in males (8.8%), ≥70 year-olds (43.8%) and residents in South region (17.7%). Mortality and case fatality rates showed a significant increase in Brazil over the period, with different patterns between regions: increasing mortality rates in the North (Annual Percent Change – APC: 9.4%; 95% confidence interval – CI: 5.3 to 13.6), and Southeast (APC: 8.1%; 95% CI: 2.6 to 13.9); and increasing case fatality rates in the Northeast (APC: 4.0%; 95% CI: 0.8 to 7.4). Spatial analysis identified a major cluster of high mortality encompassing a wide geographic range in North and Northeast Brazil.

Conclusions

Despite ongoing control strategies, mortality related to VL in Brazil is increasing. Mortality and case fatality vary considerably between regions, and surveillance and control measures should be prioritized in high-risk clusters. Early diagnosis and treatment are fundamental strategies for reducing case fatality of VL in Brazil.     

Docking of the alkaloid geissospermine into acetylcholinesterase: a natural scaffold targeting the treatment of Alzheimer’s disease

Pharmacological studies from our group [Lima et al. Pharmacol Biochem Behav 92:508, (2009)] revealed that geissospermine (GSP), the major alkaloid of the bark extract of Brazilian Geissospermum vellosii, inhibits acetylcholinesterases (AChEs) in the brains of rats and electric eels (Electrophorus electricus). However, the binding mode (i.e., conformation and orientation) of this indole-indoline alkaloid into the AChE active site is unknown. Therefore, in order to propose a plausible binding mode between GSP and AChE, which might explain the observed experimental inhibitory activity, we performed comparative automatic molecular docking simulations using the AutoDock and Molegro Virtual Docker (MVD) programs. A sample of ten crystal structures of the Pacific electric ray (Torpedo californica) TcAChE, in complex with ten diverse active site ligands, was selected as a robust re-docking validation test, and also for GSP docking. The MVD results indicate a preferential binding mode between GSP and AChE, in which GSP functional groups may perform specific interactions with residues in the enzyme active site, according to the ligand–protein contacts detected by the LPC/CSU server. Four hydrogen bonds were detected between GSP and Tyr121, Ser122, Ser200, and His440, in which the last two residues belong to the catalytic triad (Ser200···His440···Glu327). Hydrophobic and π–π stacking interactions were also detected between GSP and Phe330 and Trp84, respectively; these are involved in substrate stabilization at the active site. This study provides the basis to propose structural changes to the GSP structure, such as molecular simplification and isosteric replacement, in order to aid the design of new potential AChE inhibitors that are relevant to the treatment of Alzheimer’s disease.     

Occurrence of Natural Vertical Transmission of Dengue-2 and Dengue-3 Viruses in Aedes aegypti and Aedes albopictus in Fortaleza, Ceará, Brazil

Background

Aedes aegypti and Aedes albopictus perform an important role in the transmission of the dengue virus to human populations, particularly in the tropical and subtropical regions of the world. Despite a lack of understanding in relation to the maintenance of the dengue virus in nature during interepidemic periods, the vertical transmission of the dengue virus in populations of A. aegypti and A. albopictus appears to be of significance in relation to the urban scenario of Fortaleza.

Methods

From March 2007 to July 2009 collections of larvae and pupae of Aedes spp were carried out in 40 neighborhoods of Fortaleza. The collections yielded 3,417 (91%) A. aegypti mosquitoes and 336 (9%) A. albopictus mosquitoes. Only pools containing females, randomly chosen, were submitted to the following tests indirect immunofluorescence (virus isolation), RT-PCR/nested-PCR and nucleotide sequencing at the C-prM junction of the dengue virus genome.

Results

The tests on pool 34 (35 A. albopictus mosquitoes) revealed with presence of DENV-3, pool 35 (50 A. aegypti mosquitoes) was found to be infected with DENV-2, while pool 49 (41 A. albopictus mosquitoes) revealed the simultaneous presence of DENV-2 and DENV-3. Based on the results obtained, there was a minimum infection rate of 0.5 for A. aegypti and 9.4 for A. albopictus. The fragments of 192 bp and 152 bp related to DENV-3, obtained from pools 34 and 49, was registered in GenBank with the access codes {"type":"entrez-nucleotide","attrs":{"text":"HM130699","term_id":"297515956","term_text":"HM130699"}}HM130699 and {"type":"entrez-nucleotide","attrs":{"text":"JF261696","term_id":"340343903","term_text":"JF261696"}}JF261696, respectively.

Conclusions

This study recorded the first natural evidence of the vertical transmission of the dengue virus in populations of A. aegypti and A. albopictus collected in Fortaleza, Ceará State, Brazil, opening a discuss on the epidemiological significance of this mechanism of viral transmission in the local scenario, particularly with respect to the maintenance of these viruses in nature during interepidemic periods.     

Changes in the small intestine of Schistosoma mansoni-infected mice fed a high-fat diet

The consumption of a high-fat diet modifies both the morphology of the small intestine and experimentally tested effects of schistosomiasis mansoni. However, whether a schistosomiasis infection associated with a high-fat diet causes injury to the small intestine has never been investigated. Mice were fed either a high-fat or a standard-fat diet for 6 months and were then infected with Schistosoma mansoni cercariae. Physical characteristics of the intestinal tissue (mucosal thickness, small intestinal villi length and height, and abundance of goblet cells and enterocytes on the villous surface) and the distribution of granulomas along the intestinal segments and their developmental stage were measured at the time of sacrifice (9 or 17 weeks post-infection). The group fed a high-fat diet exhibited different granuloma stages, whereas the control group possessed only exudative granulomas. The chronically infected mice fed a high-fat diet exhibited higher granuloma and egg numbers than the acutely infected group. Exudative, exudative/exudative-productive and exudative-productive granulomas were present irrespective of diet. Computer-aided morphometric analysis confirmed that villus length, villus width, muscular height and submucosal height of the duodenal and jejunal segments were affected by diet and infection. In conclusion, a high-fat diet and infection had a significant impact on the small intestine morphology and morphometry among the animals tested.     

Feeding patterns of mosquitoes (Diptera: Culicidae) in six Brazilian environmental preservation areas

Feeding patterns of mosquitoes in six Brazilian environmental preservation areas were analyzed by the precipitin technique. The mosquito populations were captured using Shannon traps during different time periods. Bird, cow, dog, horse, opossum, human, and rodent antisera diagnostic tests were employed and results were analyzed by calculating the Sørensen similarity index and using the null‐model test. Of the 647 analyzed specimens, 443 reacted to the utilized antisera, of which 331 reacted to one blood source, with the most frequent being birds (49.4%); and 112 specimens reacted to two blood sources, with the most frequent combination from birds + rodents (14.3%). The feed profiles demonstrated that Anopheles albitarsis, An. evansae, Aedes fulvus, Psorophora albigenu, Ps. albipes, Ps. ferox, and Mansonia titillans fed predominantly on birds. The similarity index showed that in some localities An. cruzii, Chagasia fajardi, Ae. scapularis, Ae. serratus, Haemagogus leucocelaenus, Ps. albigenu, and Ps. ferox presented similar dietary habits. The null‐models test indicated that species from SMSP, INP, CGNP, and THP demonstrated an aggregate pattern, while species from SONP and SBNP showed a random pattern. The mosquitoes fed predominantly on birds, but from an epidemiological standpoint, the eclectic feeding habits were found to be constant among the mosquitoes analyzed.